Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America.
Gynecol Oncol. 2021 Nov;163(2):342-347. doi: 10.1016/j.ygyno.2021.09.009. Epub 2021 Sep 21.
Although experimental models suggest that use of beta-blockers, a common antihypertensive agent, may improve survival in ovarian cancer patients, results from clinical studies have been mixed.
We evaluated the associations of pre-diagnostic (n = 950) and post-diagnostic (n = 743) use of antihypertensive medications with survival among patients with invasive, epithelial ovarian cancer in the Nurses' Health Study (NHS; 1994-2016) and NHSII (2001-2017), with follow-up until 2018 and 2019, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) for ovarian cancer mortality according to antihypertensive medication use before and after diagnosis, considering multiple drug classes (beta-blockers, calcium-channel blockers, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors).
After adjusting for age, BMI, smoking status and tumor characteristics, pre-diagnostic use versus non-use of calcium-channel blockers was associated with higher ovarian cancer mortality (HR: 1.49; 95% CI: 1.13, 1.96), which was primarily due to polytherapy involving calcium-channel blockers (HR: 1.61; 95% CI: 1.15, 2.26). Pre-diagnostic use of beta-blockers, thiazide diuretics, or ACE inhibitors was not associated with ovarian cancer mortality. No association was observed for post-diagnostic antihypertensive medication use individually or in combination, except for lower mortality associated with polytherapy involving ACE inhibitors (HR: 0.53; 95% CI: 0.31, 0.91).
Overall, we did not find clear relationships between antihypertensive medication use and ovarian cancer mortality. However, given the limitation of the data, we cannot determine whether the association may differ by type of beta-blockers. The reasons underlying the observed associations with pre-diagnostic calcium-channel blocker use and post-diagnostic ACE inhibitor use require further investigation.
尽管实验模型表明,常用降压药β受体阻滞剂的使用可能会改善卵巢癌患者的生存,但临床研究结果却存在差异。
我们评估了在护士健康研究(NHS;1994-2016 年)和 NHSII(2001-2017 年)中,950 例浸润性上皮性卵巢癌患者的诊断前(n=950)和诊断后(n=743)使用降压药物与生存之间的关系,并分别随访至 2018 年和 2019 年。使用 Cox 比例风险模型,根据诊断前后使用降压药物的情况,考虑多种药物类别(β受体阻滞剂、钙通道阻滞剂、噻嗪类利尿剂、血管紧张素转换酶[ACE]抑制剂),估计卵巢癌死亡率的危险比(HR)。
在校正年龄、BMI、吸烟状况和肿瘤特征后,与未使用钙通道阻滞剂相比,诊断前使用钙通道阻滞剂与更高的卵巢癌死亡率相关(HR:1.49;95%CI:1.13,1.96),这主要是由于涉及钙通道阻滞剂的联合治疗(HR:1.61;95%CI:1.15,2.26)。诊断前使用β受体阻滞剂、噻嗪类利尿剂或 ACE 抑制剂与卵巢癌死亡率无关。除了涉及 ACE 抑制剂的联合治疗与较低的死亡率相关(HR:0.53;95%CI:0.31,0.91)外,未观察到诊断后使用降压药物的个体或联合治疗与卵巢癌死亡率之间存在关联。
总体而言,我们没有发现降压药物使用与卵巢癌死亡率之间的明确关系。然而,鉴于数据的局限性,我们无法确定这种关联是否可能因β受体阻滞剂的类型而异。与诊断前使用钙通道阻滞剂和诊断后使用 ACE 抑制剂相关的观察到的关联的原因需要进一步研究。